For many years, there has been a need for a way to identify and differentiate large organic particles rapidly, particularly leucocytes and other types of mammalian cells. To this end, numerous physical techniques have been proposed, and machines and processes have been developed that employ these techniques. Such techniques include chemical staining methods, chromatographic analytical methods and physical methods such as automated microscopic examination systems. All of these techniques are quite limited in their capabilities, in the population of cells that they can analyze, and in their analytical speed. More importantly, many of the techniques have been shown to be of questionable accuracy.
The present invention is directed to an apparatus and process for rapidly identifying, characterizing and differentiating cells, particularly leucocytes and other mammalian cells. It employs an analytical technique known as differential light scattering, a technique which has been shown to be capable of rapid and accurate analysis of microparticles.
The terms "identifying", "characterizing" and "differentiating" cells are used in describing the usefulness of the invention. "Identifying" means to determine what the cell is, e.g. a polymorphonuclear leucocyte, while "characterizing" describes its physical features, such as size, shape, and dielectric structure, and "differentiating" separates or distinguishes different types of cells, such as sickling red blood cells from normal red blood cells, or normal lymphocytes from abnormal lymphocytes with inclusions, or cancerous squamous cells from their normal counterparts, etc.
Various systems have been described in the published literature that employ differential light scattering techniques to analyze mammalian cell systems. Such publications include "A Flow System Multi-Angle Light-Scattering Instrument For Cell Characterization" by G. C. Salzman and others, this article appearing in the Journal of Clinical Chemistry, Vol. 21, No. 9, pgs. 1297 to 1304 (1975), and "Cell Classification by Laser Light Scattering: Identification and Separation of Unstained Leucocytes" by G. C. Salzman and others which appeared in Acta Cytologica, Vol. 19, No. 4, pgs. 374 through 377 (1975). These articles describe systems which employ a monochromatic light beam to illuminate water suspended mammalian cells, the resulting differential light scattering pattern being quite complex. For that reason, an empirical approach was employed to determine which discrete areas of the overall differential light scattering pattern could be employed to isolate a specimen population of certain characteristics from populations of other characteristics. Obviously, such empirical approaches are quite limited, both in their ability to handle various cell populations and in their ability to produce meaningful results.